Nutrient-Wide Association Study for Dementia Risks: A Prospective Cohort Study in Middle-Aged and Older Adults
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Assessment of Dietary Nutrients
2.3. Assessment of Cognition and Dementia
2.4. Covariates
2.5. Statistical Analysis
3. Results
3.1. Baseline Characteristics of Participants
3.2. Associations Between Single Nutrient and Dementia
3.3. Associations Between CNS and Dementia
3.4. Exploratory Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
BMI | Body mass index |
CI | Confidence interval |
CNS | Composite nutrient score |
ENET | Elastic net |
EWAS | Nutrient-wide association study |
FDR | False discovery rate |
FFQ | Food frequency questionnaire |
HCNS | Health Care and Nutrition Study |
HR | Hazard ratio |
HRS | Health and Retirement Study |
SCFA | Saturated short-chain fatty acid |
TICS-m | Modified Telephone Interview for Cognitive Status |
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Characteristics | Total (n = 6280) | Non-Demented (n = 5785) | Incident (n = 495) | p Value |
---|---|---|---|---|
Age (years), mean (SD) | 66.88 (10.13) | 66.28 (9.87) | 73.80 (10.49) | <0.001 |
Sex, n (%) | 0.810 | |||
Male | 2544 (40.51) | 2346 (40.55) | 198 (40.00) | |
Female | 3736 (59.49) | 3439 (59.45) | 297 (60.00) | |
Race/ethnicity, n (%) | <0.001 | |||
White/Caucasian | 4921 (78.36) | 4564 (78.89) | 357 (72.12) | |
Black/African American | 929 (14.79) | 822 (14.21) | 107 (21.62) | |
Other | 430 (6.85) | 399 (6.90) | 31 (6.26) | |
Years of education, mean (SD) | 13.21 (2.79) | 13.32 (2.71) | 11.93 (3.34) | <0.001 |
Marital status, n (%) | <0.001 | |||
Married/partnered | 4232 (67.39) | 3955 (68.37) | 277 (55.96) | |
Separated/divorced/widowed | 1791 (28.52) | 1594 (27.55) | 197 (39.80) | |
Never married | 257 (4.09) | 236 (4.08) | 21 (4.24) | |
Smoking, n (%) | 0.682 | |||
Never | 2875 (45.78) | 2654 (45.88) | 221 (44.65) | |
Past | 2678 (42.64) | 2458 (42.49) | 220 (44.44) | |
Current | 727 (11.58) | 673 (11.63) | 54 (10.91) | |
BMI categories, n (%) | <0.001 | |||
Underweight | 67 (1.07) | 54 (0.93) | 13 (2.63) | |
Normal weight | 1658 (26.40) | 1499 (25.91) | 159 (32.12) | |
Overweight | 2330 (37.10) | 2130 (36.82) | 200 (40.40) | |
Obese | 2225 (35.43) | 2102 (36.34) | 123 (24.85) | |
Number of comorbidities, mean (SD) | 2.01 (1.43) | 1.97 (1.42) | 2.44 (1.47) | <0.001 |
Score of physical activity, mean (SD) | 8.19 (6.66) | 8.39 (6.68) | 5.91 (6.00) | <0.001 |
Disability, n (%) | <0.001 | |||
No | 5462 (86.97) | 5096 (88.09) | 366 (73.94) | |
Yes | 818 (13.03) | 689 (11.91) | 129 (26.06) | |
Dietary calories (kcal/day), mean (SD) | 1770.67 (660.22) | 1764.00 (655.44) | 1848.58 (709.85) | 0.011 |
Model 1 a | Model 2 b | ||||
---|---|---|---|---|---|
Subpopulation | No. of Events/Person-Years | HR (95% CI) | p Value | HR (95% CI) | p Value |
All (n = 6280) | |||||
CNS categories c | |||||
T1 (n = 2094) | 103/14,583 | Reference | Reference | ||
T2 (n = 2093) | 157/14,248 | 1.45 (1.13, 1.86) | 0.004 | 1.43 (1.11, 1.84) | 0.005 |
T3 (n = 2093) | 235/13,609 | 1.89 (1.50, 2.39) | <0.001 | 1.80 (1.42, 2.27) | <0.001 |
Continuous CNS | 495/42,440 | 4.18 (2.94, 5.92) | <0.001 | 3.55 (2.49, 5.05) | <0.001 |
Males (n = 2544) | |||||
CNS categories c | |||||
T1 (n = 830) | 43/5651 | Reference | Reference | ||
T2 (n = 842) | 66/5726 | 1.38 (0.94, 2.05) | 0.104 | 1.32 (0.89, 1.96) | 0.162 |
T3 (n = 872) | 89/5627 | 1.65 (1.14, 2.39) | 0.007 | 1.53 (1.05, 2.21) | 0.026 |
Continuous CNS | 198/17,004 | 2.65 (1.49, 4.71) | 0.001 | 2.23 (1.24, 4.01) | 0.007 |
Females (n = 3736) | |||||
CNS categories c | |||||
T1 (n = 1264) | 60/8932 | Reference | Reference | ||
T2 (n = 1251) | 91/8522 | 1.49 (1.07, 2.07) | 0.018 | 1.55 (1.11, 2.16) | 0.010 |
T3 (n = 1221) | 146/7982 | 2.06 (1.52, 2.78) | <0.001 | 2.01 (1.48, 2.72) | <0.001 |
Continuous CNS | 297/25,436 | 5.47 (3.52, 8.49) | <0.001 | 4.58 (2.94, 7.13) | <0.001 |
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Guo, J.; Gu, Y. Nutrient-Wide Association Study for Dementia Risks: A Prospective Cohort Study in Middle-Aged and Older Adults. Nutrients 2025, 17, 1960. https://doi.org/10.3390/nu17121960
Guo J, Gu Y. Nutrient-Wide Association Study for Dementia Risks: A Prospective Cohort Study in Middle-Aged and Older Adults. Nutrients. 2025; 17(12):1960. https://doi.org/10.3390/nu17121960
Chicago/Turabian StyleGuo, Jing, and Yian Gu. 2025. "Nutrient-Wide Association Study for Dementia Risks: A Prospective Cohort Study in Middle-Aged and Older Adults" Nutrients 17, no. 12: 1960. https://doi.org/10.3390/nu17121960
APA StyleGuo, J., & Gu, Y. (2025). Nutrient-Wide Association Study for Dementia Risks: A Prospective Cohort Study in Middle-Aged and Older Adults. Nutrients, 17(12), 1960. https://doi.org/10.3390/nu17121960